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Introduction: Factor Xa inhibitor (FXaI)-associated bleeding events are common and associated with substantial morbidity. Systematic evaluation of widely available, effective, and affordable FXaI bleed management strategies is needed., Materials and Methods: We conducted a single-center retrospective cohort study of FXaI-treated patients presenting to a tertiary academic medical center from January 2018 to May 2019 who received 25-50 IU/kg 4F-PCC for either FXaI-associated major bleeding or urgent surgery. The primary outcome was hemostatic efficacy, and the safety outcome was the 30-day risk of thromboembolism., Results: PCC was used to treat FXaI-associated bleeding in 83 cases (79.1 %) and was given before urgent surgery in 22 cases (20.9 %). Sixty-six patients were on apixaban, 38 were on rivaroxaban and one patient was on edoxaban. Intracranial hemorrhage (ICH) and gastrointestinal bleeding accounted for most bleeds (74.7 %). Median interval between last DOAC intake and presentation to triage was 9 h [IQR 5.3-14.8] and median PCC dosing was 40.0 IU/kg [IQR 28.5-46.6]. Forty-two patients (40.0 %) had pre-PCC FXaI levels drawn with median FXaI levels of 114.5 ng/mL [IQR 70.0-175.0]. Effective hemostasis occurred in 66.7 % [95%CI 55.4-76.3] of patients receiving PCC for bleeding and surgical hemostasis was rated as normal in 95.5 % (95%CI 76.5-100.0) for patients having urgent surgery. The 30-day risk of thromboembolism was 7.6 % [95%CI 3.7-14.5] and 22.9 % [95%CI 15.8-31.8] of patients died., Conclusions: PCC for FXaI-associated bleeding was associated with hemostatic efficacy in two-thirds of patients and thromboembolic events were uncommon. PCC represents a promising treatment strategy for FXaI-associated bleeding., Competing Interests: Declaration of competing interest J.R. Shaw has received in-kind laboratory support from Diagnostica Stago. J.H. Levy serves on steering committees for Merck, Octapharma, Takeda, and Werfen. S. Schulman reports research grant funding from Octapharma and honoraria from Alexion, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Regeneron, Sanofi, and Takeda. D.M. Siegal has received honoraria paid indirectly to her institution from Astra Zeneca, BMS-Pfizer, Servier. D. Dowlatshahi has provided consultation to Astra Zeneca Canada. M. Carrier has received research funding from Leo Pharma and Pfizer, in addition to honoraria from BMS, Valeo Pharma, Leo Pharma, Sanofi and Servier. L. Castellucci's research institution has received honoraria from Bayer, BMS-Pfizer Alliance, The Academy for Continued Advancement in Healthcare Education, Amag Pharmaceutical, LEO Pharma, Sanofi, Valeo Pharma, and Servier., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The risk of venous thromboembolism (VTE) is 15 to 35-fold higher in the postpartum period compared to non-pregnant individuals. Clinical practice guidelines recommend the use of postpartum thromboprophylaxis with low molecular weight heparin (LMWH) for 6 weeks in individuals at high risk of developing VTE. However, a marked reduction in the risk of VTE risk occurs beyond the third week of the postpartum period., Objective: We sought to characterize practice patterns of clinicians who manage postpartum individuals at high risk of VTE., Methods: We conducted a cross-sectional study using a self-administered electronic questionnaire. The survey explored the use of postpartum thromboprophylaxis in high-risk individuals. Descriptive statistics were used to summarize survey responses., Results: Of the 113 participants that responded to the initial invitation, 78 completed the survey (Europe (53.9 %); North America (23.2 %); Australia and New Zealand (19.0 %)). For individuals with a prior unprovoked or provoked deep venous thrombosis or pulmonary embolism, cerebral vein thrombosis and splanchnic vein thrombosis, 97.4 %, 93.5 %, 91.0 % and 88.5 % of the respondents recommended six weeks of postpartum thromboprophylaxis using LMWH, respectively. The recommendation for 6 weeks of thromboprophylaxis in patients with sickle cell disease and obstetric APS was comparatively lower (70.5 and 78.2 % respectively). Respondents with higher practice volumes and more years of experience in clinical practice were more likely to recommend a shorter duration of thromboprophylaxis., Conclusion: Our study highlights the variability in clinician recommendations and the acceptability of treatment durations for postpartum thromboprophylaxis in high-risk conditions. Prospective studies are needed to determine optimal duration and establish evidence-based management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Post-thrombotic syndrome (PTS) is common in patients with deep vein thrombosis (DVT). It is unclear if different types of anticoagulant therapies (e.g. vitamin K antagonists (VKA), direct oral anticoagulants (DOACs) or low molecular weight heparin (LMWH)) are associated with different risks of PTS. We sought to assess the incidence rates of PTS development following a proximal DVT of the lower extremity managed with different types of anticoagulation regimens., Methods: A systematic search of MEDLINE, EMBASE and PubMed, from inception to June 2023 was performed. The primary outcome was development of PTS. The secondary outcomes included severe PTS, venous ulcers, and major bleeding. Incidence rates were pooled using the random effects model and expressed as event per 100 patient-years with its associated 95 % confidence intervals (CI) using R software., Results: A total of 21 (4342 patients) articles were included in the analysis. The adjusted pooled incidence of PTS was 15.1 (95 % CI: 8.7 to 26.1), 18.2 (95 % CI: 9.4 to 35.1) and 24.6 (95 % CI: 9.2 to 65.5) per 100 patient-years patients managed with VKA, DOAC and LMWH, respectively. The adjusted pooled incidence of severe PTS was 5.1 (95 % CI: 2.6 to 10.0) and 0.2 (95 % CI: 0.01 to 2.7) per 100 patient-years for VKAs and DOACs, respectively., Conclusions: The development of PTS is common in patients with proximal lower extremity DVT. The incidence rates of PTS seem to be similar across the different anticoagulation regimens, but severe PTS may be lower among patients receiving a DOAC., Competing Interests: Declaration of competing interest M. Carrier has received research funding from BMS, Pfizer, and Leo Pharma, and honoraria from Bayer, Pfizer, BMS, Servier, and Leo Pharma. A. Delluc reports grants from Leo Pharma and Pfizer, personal fees from BMS, Leo Pharma, Pfizer, Servier. C Brown and L Tokessy have no relevant conflicts of interest to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Approximately 10 % of all diagnosed pulmonary embolism are isolated to the subsegmental vessels. The risk of recurrent venous thromboembolism (VTE) in patients with an acute subsegmental pulmonary embolism (SSPE) managed with or without anticoagulant therapy remains poorly understood., Methods: This is an observational cohort study including consecutive adult patients diagnosed with acute isolated SSPE between June 01, 2019, and August 31, 2022. We excluded patients with a concomitant diagnosis of deep vein thrombosis and those who had an indication for long-term anticoagulation. The primary outcome was objectively confirmed recurrent VTE., Results: Overall, 118 patients with acute SSPE were included in the analysis. The mean (± standard deviation [SD]) age of the participants was 59 ± 17 years and 44 % of them had active cancer. Mean (±SD) duration of follow-up was 438 ± 426 days. Seventy-seven patients (65 %) were initially treated with anticoagulation, whereas 41 patients (35 %) were not. Of the 77 patients receiving anticoagulant therapy, 23 (30 %) received extended-duration anticoagulation (beyond 3 months) for secondary prevention. Overall, recurrent VTE events occurred in 6/118 (5 %, 95 % CI 2.4 to 10.7) patients. Four events (4/77 = 5.2 %, 95 % CI 2.0 to 12.6) occurred in initially treated patients. Two recurrent VTE occurred in patients initially left untreated (2/41 = 4.9 %, 95 % CI 1.4 to 16.1). Half of the recurrent VTE occurred in patients with active cancer., Conclusions: Most patients diagnosed with an acute SSPE received anticoagulation. The incidence of recurrent VTE detected over time was relatively high, especially in patients with cancer., Competing Interests: Declaration of competing interest L. Girardi, L. A. Ciuffini, V. Mai, D. Santagata and TF. Wang report no conflicts of interests. W. Ageno reports advisory board honoraria from Bayer, Boehringer Inghelheim, Daiichi Sankyo, BMS/Pfizer, Sanofi, and Portola, and reports research funding and personal fees from Bayer, and personal fees from BMS/Pfizer, Daiichi Sankyo, Sanofi, Aspen, Janssen, and Portola, outside the submitted work. M. Carrier has received research funding from BMS, Pfizer, and Leo Pharma, and honoraria from Bayer, Pfizer, BMS, Servier, and Leo Pharma. G. Le Gal reports advisory board honoraria from Inari, Pfizer, Sanofi. G. Le Gal holds a Chair on Diagnosis of Venous Thromboembolism at the Faculty of Medicine, University of Ottawa., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Economically developed countries continue to find that venous thromboembolism (VTE) is a major cause of morbidity and mortality., Objective: To compare baseline risk profiles and patient workflow patterns between the United States (U.S.) and Canadian management of VTE patients from 2014 to 2017., Methods: The Global Anticoagulant Registry in the FIELD (GARFIELD-VTE) is a prospective, observational study of 10,679 patients with objectively confirmed VTE, followed for 3 years. In total 1101 patients enrolled in the U.S. and Canada were included in this analysis., Results: Median age and body mass index were comparable between the U.S. (60.5; 30.2) and Canadian (59.7; 29) patients. A higher percentage of U.S. patients were black (n = 128, 24.1 %; n = 22, 3.9 %) and had a higher VTE-associated risk profile, including immobilization, hospitalization, and recent surgery. U.S. patients had a higher combined DVT and PE primary diagnoses (20.3 %) and were more likely to be treated in hospitals (77.2 %) than Canadians (13.3 %; 48.1 %). Direct oral anticoagulant therapy (DOAC) was nearly two-fold more frequent in Canadian patients (n = 218, 39.2 %) at the end of 3 years in comparison to the U.S. (n = 118, 23.0 %). Adjusted for sex, recent bleed event, heart failure, chronic immobilization, family history of VTE, history of cancer and prior VTE, and renal insufficiency, the risk of all-cause mortality was 51.9 % higher in patients from the U.S. compared to those in Canada after 3 years. Patients from the U.S. also had a higher likelihood of hospitalization, major bleeding, and recurrent VTE after controlling for prior history and comorbid conditions., Conclusion: Higher rates of adverse VTE-associated outcomes in the U.S. may be attributed to different baseline risk profiles, facility care, and distribution of specialists and their subsequent treatment strategies., Type of Research: Global, multicentre, non-interventional, prospective registry titled Global Anticoagulant Registry in the FIELD - Venous Thromboembolism (GARFIELD-VTE)., Key Findings: 531 U.S. and 557 Canadians patients included in study. DOAC use more frequent in Canadian patients after 3 years than U.S. (39.2 % vs. 23.0 %, respectively). Adjusted for sex, recent bleed event, heart failure, chronic immobilization, family history of VTE, history of cancer and prior VTE, and renal insufficiency, all-cause mortality risk remained higher in U.S. patients vs. Canadian patients after 3 years. U.S. patients had higher likelihood of hospitalization, major bleeding, and recurrent VTE., Take-Home Message: Higher rates of adverse VTE-associated outcomes in the U.S. may be attributed to different baseline risk profiles, facility care, and composition of specialists and their subsequent treatment strategies., Table of Contents Summary: Global, multicentre, non-interventional, prospective registry titled Global Anticoagulant Registry in the FIELD - Venous Thromboembolism (GARFIELD-VTE). Higher rates of adverse VTE-associated outcomes were observed in U.S. patients vs Canadian patients, which may be attributed to different baseline risk profiles, facility care, and distribution of specialists and their subsequent treatment strategies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Samuel Z. Goldhaber: Research Support from Bayer Pharma AG, Boehringer-Ingelheim, BMS, BTG EKOS, Daiichi, Janssen, NHLBI, Thrombosis Research Institute. Consultancy fees from Bayer Pharma AG, Boehringer-Ingelheim. Marc Carrier: Grants from Pfizer/BMS, Canadian Institutes of Health Research, grants and personal fees from Leo Pharma, Bayer, personal fees from Sanofi Aventis, Pfizer, Bristol Myers Squibb. Alexander G. G. Turpie: Honoraria from Bayer Pharma AG, Janssen. Karen Pieper: Consultancy fee from Johnson & Johnson. Professor Ajay K Kakkar: Research grants from Bayer Pharma AG and Sanofi. Personal fees from Anthos Therapeutics, Bayer Pharma AG, Sanofi S.A. Alisha Oropallo, Adrian C. Chen, Amit S. Rao, Gloria Kayani, Uma Maheshwari: None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: A main concern in the management of patients with cancer-associated thrombosis (CAT) is drug-drug interactions (DDIs) between anticoagulants and anticancer therapies. Their clinical implications remain unclear., Methods: To quantify the prevalence of DDIs and risks of recurrent venous thromboembolism (VTE) and bleeding events in patients with CAT on anticoagulation, we conducted a retrospective cohort study in patients with CAT on concurrent anticoagulants and anticancer and/or supportive care therapies. All patients were followed for 6 months from CAT diagnosis or until death (whichever occurred first). The primary outcome was the percentage of patients with anticoagulant DDIs classified as risk C, D, or X in Lexicomp® at any time during the 6 months. Secondary outcomes included recurrent VTE and clinically relevant bleeding events. We calculated the 6-month cumulative incidence of outcomes with 95 % confidence interval (CI) and compared those with and without DDIs, considering death as a competing risk., Results: Among 267 patients included, 111 (41.6 %) had DDIs with anticoagulants at any time during the study. Those on DOACs at any time had more DDIs compared to LMWH (50.9 % vs 19.3 %, p < 0.0001). The 6-month incidence was 8.2 % (95 % CI 5.3-11.9) for recurrent VTE and 6.7 % (95 % CI 4.2-10.2) for clinically relevant bleeding, with no significant differences between groups with or without DDIs., Conclusions: There are high incidences of DDIs in patients with CAT on anticoagulants, more with DOACs. DDIs classified as risk C, D, or X by Lexicomp® were not associated with recurrent VTE or bleeding events in our cohort., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: T-F. Wang reports grants from LEO Pharma Inc. Canada and advisory board honoraria from Valeo. A. Delluc reports grants from LEO Pharma Inc. Canada and Pfizer, personal fees from BMS, Leo Pharma, Pfizer, Servier. M. Carrier reports grants from BMS, LEO Pharma Inc. Canada and Pfizer, personal fees from BMS, Leo Pharma, Bayer, Pfizer, Servier and Sanofi. The other authors report no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: While several risk stratification tools have been developed to predict the risk of recurrence in patients with an unprovoked venous thromboembolism (VTE), only 1 in 4 patients are categorized as low-risk. Rather than a one-time measure, serial D-dimer assessment holds promise to enhance the prediction of VTE recurrence after oral anticoagulant (OAC) cessation., Methods: Using the REVERSE cohort, we compared VTE recurrence among patients with normal D-dimer levels (<490 ng/mL among males under age 70, <500 ng/mL in others) at OAC cessation and 1-month follow-up, to those with an elevated D-dimer level at either timepoint. We also evaluated VTE recurrence based on absolute increase in D-dimer levels between the two timepoints (e.g., ∆D-dimer) according to quartiles., Results: Among 214 patients with serial D-dimer levels measured at OAC cessation and 1-month follow-up, an elevated D-dimer level at either timepoint was associated with a numerically higher risk of recurrent VTE than patients with normal D-dimer levels at both timepoints (6.9 % vs. 4.2 % per year, hazard ratio 1.6; 95 % CI 0.9-2.7). Among women with <2 HERDOO2 criteria, a normal D-dimer level at both timepoints predicted a very low risk of recurrent VTE during follow-up (0.8 % per year, 95 % CI 0.1-2.8). Irrespective of baseline value, recurrent VTE risk was only 3 % per year (95 % CI 1.4-5.6) among patients in the lowest ∆D-dimer quartile., Conclusion: Serial normal D-dimer levels have the potential to identify patients at a low risk of recurrent VTE. In addition, ∆D-dimer, irrespective of its elevation above cutoff threshold, may predict recurrent VTE., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Drs. Xu, Khan, Kovacs, Sabri, Righini, Kahn, Anderson, Chagnon, White, Rodger and Le Gal have no conflicts of interest to report. Dr. Carrier reports research funding from BMS, Leo Pharma, and Pfizer; and honoraria from Bayer, Pfizer, BMS, Leo Pharma, Servier, and Sanofi. Dr. Wells reports speaker honoraria from BMS and Bayer Healthcare and prior grant funding from BMS/Pfizer. Dr. Crowther reports honoraria from Pfizer, CSL Behring, and Diagnostica Stago; consultation services to/served on advisory boards for Servier Canada, Asahi Kasei, and Precision Biologics; serving on the data safety monitoring board for Bayer; stock ownership in Alnylam; and holds the Leo Pharma Chair in Thromboembolism research, the funding for which is held in perpetuity at McMaster University (the interest is used to support M.A.C.'s research activities)., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Splanchnic vein thrombosis (SVT) is an uncommon manifestation of venous thromboembolism in the splanchnic venous system, with scarce evidence surrounding its management. We assessed the efficacy and safety of direct oral anticoagulant (DOAC) to low-molecular-weight heparins (LMWH), vitamin-k antagonists (VKAs), or no anticoagulation., Methods: We conducted a systematic review and meta-analysis with the primary efficacy outcome being complete recanalization of affected vessels and primary safety outcome being major bleeding. Meta-analysis was done using a random-effects model, with dichotomous outcomes being synthesized with odds ratios (ORs) and corresponding 95 % CIs., Results: Seven non-randomized and one randomized study involving 883 participants were included for analysis. DOACs were more effective than VKAs (OR = 4.33; 95 % CI: 2.4, 7.83; n = 1 study) in non-cirrhotic patients and no anticoagulation in cirrhotic patients (OR = 3.86; 95 % CI: 1.49, 10.03; n = 3 studies). DOACs had a statistically significant reduction in major bleeding compared to observation [OR = 0.09; 95 % CI: 0.03, 0.29; n = 3 studies], LMWHs [OR = 0.13; 95 % CI: 0.03, 0.29; n = 1 study] and VKAs [OR = 0.12; 95 % CI: 0.02, 0.69; n = 2 studies] in non-cirrhotic patients. No difference in major bleeding was found between DOACs and observation, LMWH, or VKAs in cirrhotic patients., Conclusion: DOACs appear to be a favorable alternative to VKAs and LMWHs in non-cirrhotic patients. This avenue of research would benefit from larger studies that adjust for SVT etiologies, patient risk factors, and overall bleeding risk., Competing Interests: Declaration of competing interest Mr. Allen Li has received funding from the University of Ottawa and is supported by the American Society of Hematology - 2022 Hematology Opportunities for the Next Generation of Research Scientists (HONORS) Award. Dr. Ali Eshaghpour is supported by the American Society of Hematology - 2023 Hematology Opportunities for the Next Generation of Research Scientists (HONORS) Award. Dr. Marc Carrier has received support from BMS, Leo Pharma, Pfizer, Bayer, Sanofi, Servier, Leo Pharma, BMS, Pfizer and Valeo. Dr. Mark Crowther has received support from AstraZeneca, Bayer, Pfizer, Alynlam, CSL Behring, Precision Biologics, Hemostasis reference laboratories, and Syneos Health. No other authors have relevant conflicts of interests to disclose. No funding was received for the conception and design of this study., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Isolated distal deep vein thrombosis (IDDVT) is a common clinical presentation of DVT. The efficacy and safety of anticoagulant therapy for the management of IDDVT in patients with cancer are unclear. We sought to assess the incidence of recurrent venous thromboembolism (VTE) and major bleeding in this patient population., Methods: A systematic search of MEDLINE, EMBASE and PubMed, from inception to June 2, 2022 was performed. The primary efficacy outcome was recurrent VTE and the primary safety outcome was major bleeding. The secondary outcomes were clinically relevant non-major bleeding (CRNMB) and mortality. The incidence rates of thrombotic, bleeding, and mortality outcomes were pooled using random effects model and expressed as events per 100 patient-months with associated 95 % confidence intervals (CI)., Results: Out of a total of 5234 articles, 10 observational studies including 8160 patients with cancer and IDDVT were included in the analysis. The incidence rate of recurrent VTE was 5.65 (95 % CI: 2.09-15.30) per 100 patient-years regardless of type and duration of anticoagulant therapy. The incidence rate of major bleeding was 4.08 (95 % CI: 2.52-6.61) per 100 patient-years. The incidence rates for CRNMB and mortality per 100 patient-years were 8.11 (95 % CI: 5.56-11.83) and 30.22 (95 % CI: 22.60-40.42.89), respectively., Conclusion: Patients with cancer and IDDVT are at high risk of developing recurrent VTE and bleeding complications (both major bleeding and CRNMB). More studies are needed to define the optimal management for this high-risk population., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: C. Brown and W Brandt do not have any conflicts. T-F. Wang reports research funding from LEO Pharma Research Foundation and advisory honoraria from Servier. A. Delluc reports grants from LEO Pharma Research Foundation and Pfizer, personal fees from BMS, Leo Pharma, Pfizer, Servier. M. Carrier reports grants from BMS, LEO Pharma Research Foundation and Pfizer, personal fees from BMS, Leo Pharma, Bayer, Pfizer, Servier and Sanofi., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Patients with cancer have an increased risk of both venous thromboembolism (VTE) requiring anticoagulation and thrombocytopenia. The optimal management is unclear. We performed a systematic review and meta-analysis to evaluate the outcomes in these patients., Methods: We searched MEDLINE, Embase, Scopus, and Cochrane Central Register of Controlled Trials from inception to February 5, 2022. Studies assessing adult patients with cancer-associated thrombosis and platelet count <100 × 10 9 /L were included. Three anticoagulation management strategies were reported: full dose, modified dose, or no anticoagulation. The primary efficacy outcome was recurrent VTE, and the primary safety outcome was major bleeding. The incidence rates of thrombotic and bleeding outcomes by anticoagulation management strategies were descriptive, and were pooled using random effects model and expressed as events per 100 patient-months with associated 95 % confidence intervals (CI)., Results: We included 19 observational cohort studies (N = 1728 patients) in the systematic review, with 10 included in the meta-analysis (N = 707 patients). Approximately 90 % of patients had hematological malignancies, with low-molecular-weight heparin being the main anticoagulant. The rates of recurrent VTE and bleeding complications were high regardless of management strategies - recurrent VTE on full dose: 2.65/100 patient-months (95 % CI 1.62-4.32), modified dose: 3.51/100 patient-months (95 % CI 1.00-12.39); major bleeding on full dose: 4.45/100 patient-months (95 % CI 2.80-7.06), modified dose: 4.16/100 patient-months (95 % CI 2.24-7.74). There was serious risk of bias in all studies., Conclusions: Patients with cancer-associated thrombosis and thrombocytopenia have high risks of both recurrent VTE and major bleeding, but current literature is significantly limited to guide the best management., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: T-F. Wang reports research funding from Leo Pharma and advisory honoraria from Servier. M. Carrier reports grants from BMS, Leo Pharma and Pfizer, personal fees from BMS, Leo Pharma, Bayer, Pfizer, Servier and Sanofi. B.J. Carney reports personal fees from Sanofi. A. Delluc reports grants from Leo Pharma and Pfizer, personal fees from BMS, Leo Pharma, Pfizer, Servier., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Venous thromboembolism (VTE) is a leading cause of mortality in patients with cancer and is associated with significant morbidity and healthcare expenditure. The risk of VTE is increased following the insertion of a central venous catheter (CVC) for chemotherapy delivery and supportive care. The risks and benefits of primary thromboprophylaxis in patients with cancer and CVC are unclear., Objective: We sought to assess the rates of VTE and bleeding complications and to determine the efficacy and safety of primary thromboprophylaxis in adult patients with cancer and a CVC., Methods: A systematic search of MEDLINE, EMBASE, and all EBM was conducted. Randomized controlled trials (RCTs) of adult patients with cancer and a CVC receiving primary thromboprophylaxis compared to observation/placebo were included. The primary efficacy and safety outcomes were total VTE and major bleeding episodes, respectively., Results: A total of 12 RCTs (3545 patients) were included in the analysis. The total rates of VTE were significantly lower in patients receiving thromboprophylaxis compared to those not receiving primary prevention (7.6% vs. 13%; Odds Ratio (OR) 0.51, 95% CI 0.32-0.82, p < 0.01). The rates of major bleeding complications were not higher in patients receiving thromboprophylaxis (0.9% vs. 0.6%; OR 1.12, 95% CI 0.29-4.40, p = 0.87)., Conclusions: Primary thromboprophylaxis significantly reduced the risk of VTE without increasing the risk of major bleeding complications in patients with cancer and CVC. Future studies are needed to confirm these findings., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Postoperative venous thromboembolism (VTE) is a significant source of morbidity and mortality in cancer patients undergoing major abdominopelvic surgery. Many guidelines recommend the use of extended duration postoperative low molecular weight heparin (LMWH) thromboprophylaxis, although the evidence for its overall safety and efficacy is unclear., Aims: We sought to assess the 30-day postoperative rates of VTE and bleeding complications following major abdominopelvic cancer surgery and to explore the potential risks and benefits of extended duration thromboprophylaxis with LMWH in such setting., Methods: A systematic search of the literature was conducted. Observational studies and RCTs of adult patients that underwent abdominopelvic cancer surgery were included. Pooled proportions for the outcome measures and pooled relative risks for the extended duration thromboprophylaxis analyses were generated., Results: A total of 68 studies (1,631,118 patients) were included in the analysis. The 30-day postoperative rate of VTE was 1.7% (95%CI: 1.5 to 1.9, I 2  = 98%). The postoperative rate of clinically-relevant bleeding complications was 3.5% (95%CI: 1.6 to 6.1, I 2  = 99%). Extended duration thromboprophylaxis was associated with a significant reduction in the incidence of clinical VTE (1.0% vs 2.1%; Risk ratio (RR) 0.48, 95%CI: 0.31 to 0.74; I 2  = 0), without a significant increase in clinically-relevant bleeding (4.0% vs. 4.9%; RR 1.0, 95%CI: 0.66 to 1.5, I 2  = 0)., Conclusions: The overall risk of symptomatic VTE within 30 days of surgery was relatively low. Extended LMWH thromboprophylaxis following major abdominopelvic cancer surgery was associated with a reduced incidence of clinical VTE without an increase in clinically-relevant bleeding., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Venous thromboembolism (VTE) is a common complication after intracranial hemorrhage (ICH); the incidence has been reported to vary between 18% to 50% for deep vein thrombosis and between 0.5% to 5% for pulmonary embolism (PE). According to current clinical practice guidelines, patients with acute VTE should receive anticoagulant treatment for at least 3 months in the absence of contraindications. Anticoagulant treatment reduces mortality, prevents early recurrences and improves long-term outcome in patients with acute VTE. However, recent ICH is an absolute contraindication for anticoagulant treatment due to the potential increased risk of hematoma expansion or recurrent ICH. Hematoma expansion occurs in approximately a third of patients within 24 h following the diagnosis of a spontaneous ICH. The risk for recurrent ICH depends on patients' features as well as on the feature of index ICH. Limited evidence is available on the risks of therapeutic anticoagulation started shortly after ICH. Expert consensus around the introduction of therapeutic anticoagulation suggests delaying therapeutic anticoagulation for at least 2 weeks after spontaneous ICH, until the risk re-bleeding becomes acceptable. Vena cava filters should be inserted to reduce the risk for (non) fatal PE until therapeutic anticoagulation can be started; antithrombotic prophylaxis should be started as soon as possible to avoid recurrent VTE after vena cava filter insertion. For patients presenting PE with hemodynamic compromise, percutaneous embolectomy should be considered. Most patients will be able to receive anticoagulant treatment within 4 weeks following spontaneous ICH; direct oral anticoagulants are probably the treatment of choice for those ICH patients tolerating anticoagulant treatment., (Copyright © 2021. Published by Elsevier Ltd.)

Introduction: Risk assessment models are used to stratify cancer patients according to their underlying risk of VTE. The CATS score has been shown to enhance VTE risk stratification as compared to the modified Khorana score by incorporating d-dimer and soluble p-selectin measurements. Our aim was to evaluate the performance of the CATS score with respect to VTE risk stratification., Materials and Methods: Analysis of a subset of the AVERT trial population for whom biomarker data was available. All patients included in the AVERT trial were at increased risk of VTE based on a modified Khorana score of ≥2. Patients were stratified according to the modified Khorana score and CATS score. Kaplan-Meier analysis was used to calculate the 6-month cumulative probabilities of VTE., Results: A total of 466 patients were included in the analysis, 229 and 237 patients in the placebo and apixaban arms, respectively. The 6-month cumulative probability of VTE among patients with a modified Khorana score ≥ 3 was 13% [95% CI 7 to 23], whereas it was 20% [95% CI 11 to 35] for patients with a CATS score ≥ 4. The absolute risk reduction achieved with apixaban VTE prophylaxis among patients with modified Khorana ≥2, modified Khorana ≥3 and CATS ≥4 was -5.9% [-10.9 to -0.8], -5.8% [-16.0 to 4.5] and -10.1% [-22.9 to 2.6], respectively. Apixaban VTE prophylaxis among patients with increasing modified Khorana or CATS scores was not associated with an increased risk of bleeding events., Conclusions: The use of a CATS score of ≥4 to identify ambulatory cancer patients at very high risk of VTE could enhance the benefit/risk ratio achieved with apixaban VTE prophylaxis., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Studies evaluating the use of activated prothrombin complex concentrates (aPCCs) for DOAC-associated bleeding are sparse., Materials and Methods: We conducted a retrospective study of patients receiving aPCC for DOAC-associated bleeding or for pre-operative optimization of hemostasis prior to urgent surgery. The primary efficacy outcome was hemostatic efficacy, the primary safety outcome was the 30-day thromboembolic complication rate., Results: Eighty-two patients were included in the analysis; 14 patients on dabigatran, 39 patients on rivaroxaban and 29 patients on apixaban. Fifty-four patients received aPCC for major bleeding and 28 patients prior to urgent surgery. Mean aPCC dosing was 2974 IU (SD ± 857 IU). Hemostasis was deemed effective by ISTH criteria in 50% of cases and "Good" or "Moderate" by Sarode criteria in 45.2% and 14.3% of cases, respectively. Surgical hemostasis was rated as "Normal" in 84% of cases pre-operative administration. Median pre-aPCC INR was 1.6 (IQR 0.5) and median post-aPCC INR was 1.2 (IQR 0.2) (p < 0.00001). Median pre-aPCC aPTT was 36 s (IQR 12.8), median post-aPCC aPTT was 29 s (IQR 9.8) (p = 0.0001). The 30-day thromboembolic event rate was 6.1%., Conclusion: Further study is needed to characterize the hemostatic effects and thromboembolic risk of aPCC among patients with DOAC-associated bleeding or for attempted normalization of hemostasis prior to urgent surgery., (Copyright © 2020. Published by Elsevier Ltd.)

Objective: The therapeutic effects of low molecular weight heparins (LMWH) may extend past thrombosis prevention, with preclinical evidence demonstrating anti-metastatic properties. Clinical evidence on the topic, however, remains controversial. A systematic review of preclinical evidence may help elucidate reasons for this contradictory evidence. The objective of our systematic review is to assess the anti-metastatic properties of LMWHs in solid tumour animal models., Methods: MEDLINE, Embase, Web of Science and PubMed were searched from inception to May 12th, 2020. All articles were screened independently and in duplicate. Studies that compared LMWH to a placebo or no treatment arm in solid tumour animal models were included. The primary outcome was the burden of metastasis. Secondary outcomes included primary tumour growth and mortality. The risk of bias was assessed in duplicate using a modified Cochrane Risk of Bias tool., Results: Forty-two studies were included in the review. Administration of a LMWH was associated with a significant decrease in the burden of metastasis (SMD -2.18; 95% CI -2.66 to -1.70). Additionally, the administration of a LMWH was also associated with a significant reduction in primary tumour growth (SMD -1.95; 95% CI -2.56 to -1.34) and risk of death (RR 0.39; 95% CI 0.16-0.97). All included studies were deemed to be at an unclear risk of bias for at least one methodological criterion., Conclusions: Our results demonstrate that LMWH can effectively reduce metastatic burden and reduce tumour growth in preclinical animal models of solid tumour malignancies. Reasons for the contradiction with clinical evidence require further exploration., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Venous thromboembolism (VTE) is a life-threatening, yet potentially preventable, complication of inflammatory bowel disease (IBD). The incidence of VTE in IBD is roughly three-fold greater than in the general population, and results in a 2-fold increased risk of mortality. The absolute risk is highest during hospitalization and has led to consensus guidelines recommending thromboprophylaxis for all admitted patients with IBD in the absence of contraindications. Emerging evidence suggests that the risk of VTE is likely to remain high early after hospital discharge. Despite this, it remains unclear if thromboprophylaxis should be continued after hospitalization. Therefore, this review will synthesize the available literature pertaining to the post-discharge setting with a focus on the incidence of VTE, associated risk factors, and the potential role for extended thromboprophylaxis., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The mechanisms surrounding cancer-associated venous thromboembolism (VTE) are not well characterized. AVERT, a randomized placebo controlled thromboprophylaxis study in ambulatory cancer patients, provides a unique opportunity to gain insights into thrombotic mechanism(s)., Methods: All available citrated platelet-free plasma samples collected at the point of randomization from individuals enrolled in the AVERT study were evaluated for the expression of D-dimer, soluble P-selectin (sP- selectin), active plasminogen activator inhibitor 1 (aPAI-1), clot lysis time (CLT) and activated factor XIa-C1 inhibitor complex (FXIa-C1). We compared the differential expression of sP-selectin, aPAI-1, CLT and FXIa-C1 among individual tumor types with normal controls. We evaluated the impact of disease type (hematologic versus solid organ malignancy) and stage (metastatic versus non-metastatic) on individual biomarker expression., Results: We included 449 AVERT participants in this analysis. Baseline expression of the selected thrombosis biomarkers differed significantly by individual tumor type compared with normal controls. Levels of aPAI-1, CLT, FXIa-C1 and sP-selectin were significantly elevated in individuals with lymphoma compared to individuals with non-metastatic solid organ malignancies (p<0.05). Individuals with metastatic solid organ disease had elevated levels of D-dimer and sP-selectin compared to those with non-metastatic disease (p<0.05)., Conclusion: Among a cohort of ambulatory patients at intermediate to high risk of VTE, these exploratory findings suggest that baseline activation of coagulation and fibrinolysis pathways vary significantly by tumor type and disease stage., Competing Interests: Conflict of interest statement M.C. reports receiving grant support and honoraria from Leo Pharma and Bayer and honoraria from Sanofi-Aventis, Pfizer, and Bristol-Myers Squibb. P.W. reports receiving grant support, lecture fees, and advisory board fees from Bayer HealthCare, lecture fees from Medscape, Pfizer, and Daiichi Sankyo, fees for serving on a writing committee from Itreas, grant support from Bristol-Myers Squibb/ Pfizer, consulting fees from Janssen Scientific, and fees for serving on a roundtable from Sanofi. No other potential conflict of interest relevant to this article was reported., (© 2020 Elsevier Ltd. All rights reserved.)

Suspected recurrent venous thromboembolism (VTE) is a common and vexing clinical problem. Confounding the diagnosis of recurrent VTE is a high frequency of residual VTE from prior VTE. The diagnosis of recurrent VTE must be established by comparing current imaging with past imaging to distinguish acute from chronic thrombosis. Next, we must ascertain if non-compliance was the cause of "apparent therapeutic failure" and if non-compliance is at play then re-initiate anticoagulant therapy. Therapeutic failure is relatively uncommon. As such, we must consider underlying causes of therapeutic failures including malignancy and potent thrombophilias. Finally, short term anticoagulant management of therapeutic failures is controversial, and requires further research, but the best current evidence supports a course of full-dose low-molecular-weight heparin (LMWH) (and dose escalated LMWH if failure occurs while on full-dose LMWH)., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Implanted vascular access devices (IVADs) have significantly improved the management of cancer patients. These patients are at an increased risk of venous thromboembolism and IVADs are a known risk factor. We sought to assess the incidence of IVAD-related upper extremity deep vein thrombosis (IVAD-related UEDVT) associated with BioFlo® IVADs (Angiodynamics, Inc.)., Methods: A total of 394 cancer patients were enrolled over 12 months. The primary outcome was the incidence of IVAD-related UEDVT confirmed by diagnostic imaging. IVAD-related UEDVT was defined as symptomatic ipsilateral upper extremity (axillary vein or proximal) deep vein thrombosis and symptomatic pulmonary embolism (PE). Patients were followed until initiation of therapeutic anticoagulation, catheter removal, death, or up to 12 months., Results: 389 patients were included in the analysis. The median age of the cohort was 58.2 years; 68% (n = 273) were females. Sixty-six percent had gastrointestional cancer (including pancreatic cancer) and 68% had metastases. Eighty four percent of IVADs were right sided insertions. Ninety eight percent of catheter tip placements were distal superior vena cava (n = 237), cavo-atrial junction (n = 67) or atrium (n = 90). Overall, 5 patients had symptomatic IVAD-related UEDVT (1.29%, 95% CI 0.2 to 2.4%)., Conclusion: IVAD-related UEDVT is an infrequent complication in cancer patients with BioFlo® IVADs., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Venous thromboembolism (VTE) is both common and a potential contributor to symptom burden in patients receiving palliative and end-of-life care. Many of the VTE treatment and prophylaxis recommendations are drawn from data of clinical trials assessing conventional VTE and cancer-associated thrombosis that excluded patients receiving specialist palliative or hospice care. In this group, the epidemiology of VTE and associated outcomes, as well as the risks and benefits of treatment in keeping with a palliative approach are of growing clinical and research interest. This narrative review summarizes current knowledge and challenges in the management of thromboembolic disease in palliative care, highlighting the complexity of decisions surrounding VTE treatment and prophylaxis., (Copyright © 2018. Published by Elsevier Ltd.)

Introduction: It is unclear if direct oral anticoagulants (DOACs) are effective and safe alternatives to low-molecular-weight heparin (LMWHs) for the treatment of cancer-associated venous thromboembolism (VTE). We aim to synthesize existing literature that compared DOACs versus LMWHs in this high-risk population., Materials and Methods: We conducted a systematic review using EMBASE, MEDLINE and CENTRAL for all observational studies and randomized controlled trials (RCTs) (PROSPERO: CRD42017080898). Two authors independently reviewed study eligibility, extracted data, and assessed bias. Primary outcomes included 6-month recurrent VTE and major bleeding. Secondary outcomes included clinically relevant non-major bleeding (CRNMB) and mortality., Results: We screened 426 articles, reviewed 25 in full-text, and selected 13 and 2 for qualitative and quantitative synthesis, respectively. Based on a meta-analysis of the 2 RCTs, DOACs had lower 6-month recurrent VTE (42/725) when compared to LMWH (64/727) (RR: 0.65 (0.42-1.01)). However, DOACs had higher major bleeding (40/725) when compared to LMWH (23/727) (RR 1.74 (1.05-2.88)). Similarly, CRNMB was higher (RR 2.31 (0.85-6.28)) for patients receiving DOACs. There was no difference in mortality (RR 1.03 (0.85-1.26)). Observational studies were heterogeneous with high risks of bias but showed recurrent VTE rates consistent with the meta-analysis., Conclusions: DOACs were more effective than LMWHs to prevent recurrent VTE but were associated with a significantly increased risk of major bleeding as well as a trend toward more CRNMB. The absolute risk differences were small (2-3%) for both primary outcomes and may reflect better compliance with DOACs than LMWHs., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Unprovoked venous thromboembolism (VTE) may be the first manifestation of an underlying cancer. We aimed to determine whether extensive screening for occult cancer in patients with unprovoked VTE was effective in reducing overall mortality among VTE patients included in prospective cancer screening studies., Methods: This pre-specified analysis of a systematic review and individual patient data meta-analysis included prospective studies comparing extensive screening with limited screening strategies for detection of occult malignant disease in unprovoked VTE patients. Overall mortality was calculated and compared according to the allocated screening strategies., Results: Among 1830 included patients, occult cancer was detected either at screening or during a 2-year follow-up period in 98 (5.4%, 95% CI 4.4 to 6.5). Twenty-seven out of the 56 patients (48.2%) diagnosed with cancer in the extensive screening group died during follow-up as compared with 23 out of 42 patients (54.8%) in the limited screening group (HR, 0.83; 95% CI, 0.48-1.45). Subgroup analyses according to time of cancer diagnosis (i.e. at screening vs. during follow-up) and according to whether cancer was diagnosed by limited screening or more extensive testing yielded similar results., Conclusion: In this individual patient data meta-analysis of clinical trials on limited vs. extensive screening, extensive screening for occult malignancy in patients with unprovoked VTE was not effective in reducing overall mortality. Diagnosing an occult cancer in unprovoked VTE patients was associated with a poor outcome., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Anticoagulation with unfractionated heparin (UFH) or low molecular weight heparin (LMWH) is the mainstay for the treatment of patients with acute cerebral vein thrombosis (CVT) with or without intracranial hemorrhage (ICH)., Aim: We conducted a systematic review and meta-analysis to determine the efficacy and safety of LMWH compared to UFH for the treatment of acute CVT., Methods: An electronic search of MEDLINE, Pubmed, CENTRAL and Google Scholar was performed. Randomized controlled trials (RCT) reporting on the efficacy and safety of anticoagulation for acute treatment of CVT were included. Outcomes of interest included mortality, disability, new ICH and pulmonary embolism (PE)., Results: Overall, 4 RCTs were included in the meta-analysis. Two trials compared anticoagulation (UFH (N = 1) and LMWH (N = 1)) to placebo. The use of anticoagulation therapy was associated with an odd ratio (OR) for mortality and disability of 0.31 (95% confidence interval (CI) 0.07 to 1.45; p = 0.14) and 0.3 (95% CI 0.09 to 1.01; p = 0.05), respectively. Three new ICHs were observed among patients receiving placebo and no patient had a PE complication. The other two trials compared LMWH to UFH. LMWH was associated with an OR for mortality and disability of 0.21 (95% CI 0.02 to 2.44, p = 0.21) and 0.5 (95% CI 0.11 to 2.23; p = 0.36), respectively. There were no new events of ICH or PE., Conclusion: LMWH seems to be safe and effective for the management of acute CVT., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Patients with active cancer have a heightened risk of venous thromboembolism (VTE). This risk is further increased by the initiation of chemotherapy. Although previous studies have suggested that the use of parenteral thromboprophylaxis in all ambulatory cancer patients receiving chemotherapy significantly decreases the rate of VTE, current clinical practice guidelines do not recommend routine use of thromboprophylaxis in this patient population. A major criticism of these studies has been the inclusion of patients at lower risk for VTE, which may have diluted the potential beneficial effect of the parenteral thromboprophylaxis. It is therefore imperative to appropriately risk stratify ambulatory cancer patients using a validated scoring system (e.g. Khorana risk score) in order to identify those most likely to benefit from thromboprophylaxis. Direct oral anticoagulants, such as apixaban, may offer a convenient and safe option for thromboprophylaxis. As such, AVERT will randomize 574 ambulatory cancer patients receiving chemotherapy who are at high-risk for VTE (as defined by a Khorana score of ≥2) to Apixaban 2.5 mg BID versus placebo. The primary study outcome will be the first episode of objectively documented symptomatic or incidental VTE (deep vein thrombosis and/or pulmonary embolism) within the first 6 months (180 days ± 3) following initiation of the blinded study drug for both intervention and placebo groups. The secondary safety outcomes include major bleeding, clinically relevant non-major bleeding, and overall survival rates. This study will hopefully offer evidence regarding the benefit of apixaban in ambulatory patients at high risk for VTE receiving chemotherapy., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Unprovoked venous thromboembolism (VTE) can be the first manifestation of an unknown cancer. A recently published individual patient data meta-analysis (IPDMA) reported a prevalence of occult cancer detection of 5.2% (95% CI, 4.1% to 6.5%) over a one-year follow-up period, approximately 50% lower than the previously reported 12-month period prevalence. Although an extensive screening strategy was associated with a 2-fold higher probability of cancer detection at initial screening in the IPDMA, not enough evidence exists yet to support the routine use of these tests in patients with unprovoked VTE. It is likely that a subgroup of patients with unprovoked VTE is at higher risk of occult cancer detection and might benefit from closer clinical surveillance. A newly derived and validated clinical predictive rule seems to be able to stratify patients with unprovoked VTE accordingly to their underlying risk of occult cancer detection. The low incidence of occult cancer detection (<3%) in the low-risk group is reassuring for clinicians. Future studies are required to better define the risks and benefits of an extensive occult cancer screening strategy in high risk patients sub-group with unprovoked VTE. To date, the Scientific and Standardized Committee from the International Society of Thrombosis and Haemostasis suggests that patients with unprovoked VTE should only undergo a limited cancer screening including thorough medical history and physical examination, basic laboratory investigations, chest X-ray as well as age- and gender-specific cancer screening according to national guidelines., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The risk of recurrent venous thromboembolism (VTE) in cancer patients despite anticoagulant therapy is high. Clinical factors and pro-coagulant markers may identify high-risk patients and guide decisions about intensifying anticoagulation therapy., Aims: To evaluate whether serial measurements of pro-coagulant markers can identify patients at high risk of recurrent VTE., Methods: In this multicenter, prospective cohort study, patients with active cancer and acute deep vein thrombosis or pulmonary embolism were enrolled. Patients received standard low-molecular-weight heparin therapy and were followed for 6 months. D-dimer and soluble P-selectin levels were measured at baseline and 1, 4, 5, 12, and 24 weeks post treatment initiation. The association between recurrent VTE and a previously developed risk score, baseline values of the biomarkers, and individual relative changes from baseline were assessed., Results: We enrolled 117 cancer patients (22% lung, 21% colorectal, 9% breast) with a mean age of 63 years; 62% had metastatic cancer. Eleven patients (9.4%) developed recurrent VTE, including two cases of fatal pulmonary embolism. VTE recurrence rates were 7.8% (95% CI, 3.1-18) in patients with a risk score of ≤0 points compared to 11% (95% CI, 5.2-20) for those with a score of ≥1 point (hazard ratio 1.3; 95% CI, 0.39-4.5). Baseline P-selectin levels but not D-dimer levels were significantly associated with a high risk of recurrence; the risk was four-fold higher in patients with elevated P-selectin levels than in those with normal levels (hazard ratio 4.0; 95% CI, 1.1-14). Changes in biomarker levels during treatment were not associated with recurrent VTE., Conclusion: Baseline P-selectin but not D-dimer levels predict recurrent VTE and may be a valuable addition to clinical prediction rules to select patients for more intensive therapy or closer observation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

There are physiologic ties between Von Willebrand Factor (VWF) and circulating tumor cells. VWF appears to play a role in tumor biology, but it is unclear whether cancer behavior differs in Von Willebrand Disease. In patients presenting with venous thromboembolism (VTE), occult cancer is frequently considered as an underlying cause. The prevalence of occult cancer after provoked VTE is low (3%); therefore, cancer screening in these patients is not routinely recommended. In those with unprovoked VTE, occult cancer is more prevalent, estimated between 4 and 10%. Due to this elevated risk, occult cancer screening is recommended in this population. Multiple studies have investigated whether a "limited" approach (including history and physical exam, basic labs, and chest X-ray) versus "extensive" approach (addition of advanced imaging, such as computer tomography) is more effective. Current data fails to demonstrate extensive screening strategies diagnose more occult cancer, miss fewer cancers during follow up, or improve cancer-related mortality. Furthermore, many patients may be needlessly exposed to unnecessary diagnostic procedures with their associated complications and costs, as well as significant anxiety. Therefore, the decision to perform additional testing should be made on a case-by-case basis. Additional studies are needed to identify subgroups of patients with unprovoked VTE at highest risk for occult cancer., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Several barriers exist for training and retention of clinician scientists, including difficulty in navigating research-related tasks in the workplace and insufficient mentorship., Objective: Our aim was to identify what core research knowledge and skills are important for the success of clinician scientists in thrombosis research, and trainees' perceived confidence in those skills, in order to develop a targeted educational intervention., Methods: A pre-tested online survey was administered to trainees and research faculty of the Canadian thrombosis research network, CanVECTOR, between September 2016 and June 2017. The importance (research faculty) and confidence (trainees) of 45 research knowledge/skills were measured using a 5-point Likert scale., Results: The survey response rate was 49% (28/57) for research faculty and 100% (10/10) for trainees. All research faculty rated developing a good research question, grant writing and writing strategies for successful publication as 'very' or 'extremely' important for trainees to learn to better transition in becoming independent researchers. Other important areas included practical aspects of research. A qualitative thematic analysis of open text responses identified 'time management' and 'leadership and teamwork' as additional important research skills. Confidence reported for each topic varied across trainees. There were three research knowledge and/or skills that ≥75% of research faculty deemed highly important and ≥50% of trainees reported lacking confidence in: grant writing, the peer-review grant process, and knowledge translation strategies., Conclusions: Developing a good research question, communicating research ideas and results and the practical aspects of research are important areas to focus future efforts in thrombosis research training., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The optimal duration of oral anticoagulant therapy after a first, unprovoked venous thromboembolism is controversial due to tightly balanced risks and benefits of indefinite anticoagulation. Risk stratification tools may assist in decision making., Objectives: We sought to determine the relationship between residual pulmonary embolism assessed by baseline ventilation-perfusion scan after completion of 5-7months of oral anticoagulant therapy and the risk of recurrent venous thromboembolism in patients with the first episode of unprovoked pulmonary embolism., Methods: We conducted a multicentre prospective cohort study of participants with a first, unprovoked venous thromboembolism enrolled after the completion of 5-7months of oral anticoagulation therapy. The participants completed a mean 18-month follow-up. Participants with pulmonary embolism had baseline ventilation-perfusion scan before discontinuation of oral anticoagulant therapy and the percentage of vascular obstruction on baseline ventilation-perfusion scan was determined. During follow-up after discontinuation of oral anticoagulant therapy, all episodes of suspected recurrent venous thromboembolism were independently adjudicated with reference to baseline imaging., Measurements and Main Results: During follow-up, 24 of 239 (10.0%) participants with an index event of isolated pulmonary embolism or pulmonary embolism associated with deep vein thrombosis and central assessment of percentage of vascular obstruction on baseline ventilation-perfusion scan had confirmed recurrent venous thromboembolism. As compared to participants with no residual pulmonary embolism on baseline ventilation-perfusion scan, the hazard ratio for recurrent venous thromboembolism was 2.0 (95% CI 0.5-7.3) for participants with percentage of vascular obstruction of 0.1%-4.9%, 2.1 (95% CI 0.5-7.8) for participants with percentage vascular obstruction of 5.0%-9.9% and 5.3 (95% CI 1.8-15.4) for participants with percentage vascular obstruction greater than or equal to 10%., Conclusions: Residual pulmonary embolism assessed by pulmonary vascular obstruction on baseline ventilation-perfusion performed after 5-7months of oral anticoagulant therapy for the first episode of unprovoked pulmonary embolism was associated with a statistically significant higher risk of subsequent recurrent venous thromboembolism. Percentage of pulmonary vascular obstruction assessment by ventilation-perfusion scans maybe a useful tool to help guide the duration of oral anticoagulant therapy after a first unprovoked pulmonary embolism., Trial Registration: Registered at www.clinicaltrials.gov identifier: NCT00261014., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In this narrative review, the epidemiology, diagnosis, prevention strategies, and management of catheter-related thrombosis are outlined. Central venous catheters have significantly improved the quality of life of patients requiring chemotherapy, parenteral nutrition, and chronic transfusions. Catheter-related thrombosis (CRT) complicates between 1-5% of inserted catheters, with incidence varying between patient population, catheter type, and vein cannulated. Strategies to prevent CRT, including anticoagulation and locking solutions, have largely been ineffective. Using clinical decision tools and D-dimer testing can limit radiographic testing for patients with suspected CRT. Although most patients with CRT are treated with anticoagulation, the most effective type and duration of treatment have not been established for adults or children. Many unanswered questions remain concerning risk stratification, prevention, and management of CRT. National and international collaborative research networks could be harnessed to perform these much needed studies., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Venous thromboembolism (VTE) is a common complication among patients with glioma. However, data on the safety of therapeutic doses of anticoagulation is scarce in this patient population., Objectives: The purpose of this study is to evaluate the risk of intracranial hemorrhage (ICH) in glioma patients receiving therapeutic anticoagulation for VTE treatment., Patients and Methods: We conducted a case-control study including glioma patients with and without acute VTE from Jan 2010 to March 2015. Controls were matched based on age, gender and tumor grade., Result: 569 patients with glioma were identified, 76 (13.3%) developed acute VTE. Of the 70 patients treated with full dose anticoagulant therapy, 14 (20%) patients had a major bleeding including 11 (15.7%) ICH. The odds ratio for ICH in patients with glioma and VTE who were treated with anticoagulation compared to the control group was 7.5 (95% CI, 1.6-34.9) p=0.01. Overall survival was similar for VTE and control group (36 vs. 42months, p=0.93)., Conclusion: Therapeutic anticoagulation is associated with a 7-fold increase risk of ICH in glioma patients. Data emerging from this study support the need for high quality studies to evaluate the risk of ICH in patients with glioma and VTE., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Cancer patients appear to be at increased risk for atrial fibrillation. Although surgery and chemotherapy exacerbate this risk, this association is observed even in the absence of any cancer-specific treatment. The underlying mechanism of this is likely multifactorial, but systemic inflammation and autonomic dysregulation are hypothesized to play critical roles. Cancer and atrial fibrillation are both independent risk factors for ischemic stroke; however, it is not clear whether this translates to an increased risk of stroke in patients with both comorbidities. As such, commonly used risk stratification tools including the CHADS2 score currently do not take cancer into account as a variable and it is possible that stroke risk is underestimated in this population. There is a paucity of data regarding anticoagulant choice in cancer patients with atrial fibrillation. Vitamin K antagonists are often preferred over direct oral anticoagulants; however, this may be changing in the near future as new trials specific to this patient population emerge., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Patients with unprovoked venous thromboembolism (VTE) should receive anticoagulant treatment for at least 3 to 6months. Thereafter, the decision to extend treatment indefinitely for secondary prevention of recurrent events is based on a personalized assessment of the risks of recurrent VTE and anticoagulant-related bleeding. Whereas there are clinical factors that identify patients at higher risk of recurrent VTE, factors to aid the prediction of major bleeding events during anticoagulant therapy have received much less attention. It is now clear that establishing an accurate estimate of the risk of major bleeding is required in treatment decision making. Several studies aimed at deriving new, or validating existing, clinical prediction scores for major bleeding in patients with VTE have been published. The aim of this review is to provide an overview of the available clinical prediction scores, highlighting the methodological shortcomings with their derivation and validation, summarize their performance, and provide considerations for bleeding risk assessment in clinical practice., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Importance: Unprovoked venous thromboembolism (VTE) can be the first manifestation of cancer. It is unclear if extensive screening for occult cancer including a comprehensive computed tomography (CT) scan of the abdomen/pelvis is cost-effective in this patient population., Objective: To assess the health care related costs, number of missed cancer cases and health related utility values of a limited screening strategy with and without the addition of a comprehensive CT scan of the abdomen/pelvis and to identify to what extent testing should be done in these circumstances to allow early detection of occult cancers., Participants and Setting: Cost effectiveness analysis using data that was collected alongside the SOME randomized controlled trial which compared an extensive occult cancer screening including a CT of the abdomen/pelvis to a more limited screening strategy in patients with a first unprovoked VTE, was used for the current analyses., Main Outcomes and Measures: Analyses were conducted with a one-year time horizon from a Canadian health care perspective. Primary analysis was based on complete cases, with sensitivity analysis using appropriate multiple imputation methods to account for missing data., Results: Data from a total of 854 patients with a first unprovoked VTE were included in these analyses. The addition of a comprehensive CT scan was associated with higher costs ($551 CDN) with no improvement in utility values or number of missed cancers. Results were consistent when adopting multiple imputation methods., Conclusions and Relevance: The addition of a comprehensive CT scan of the abdomen/pelvis for the screening of occult cancer in patients with unprovoked VTE is not cost effective, as it is both more costly and not more effective in detecting occult cancer., (Copyright © 2017 Elsevier Ltd. All rights reserved.)